PROJECT SUMMARY/ABSTRACT Anterior Cruciate Ligament (ACL) injury is a proven high-risk factor for post-traumatic osteoarthritis (PTOA) development despite ACL reconstruction (ACLR). However, our understanding of PTOA development after ACLR is limited, and reliable ?markers? (risk factors) that provide early diagnosis and prognosis are still lacking. Long-term studies of PTOA after ACLR primarily used radiographs for evaluating structural damage, which only provided information limited to bone changes that occur at late stages of the disease. Previous MRI studies after ACLR are primarily limited to short/mid-term follow up. The long-term degeneration of soft tissue, their relationship to each other, and to patient symptoms and outcomes after ACLR are largely unknown. In this study, we aim to fill this gap and propose to add morphologic and quantitative MRI (qMRI) to the novel nested cohort from the Multicenter Orthopaedic Outcomes Network (MOON) at 10 years after ACLR. The NIH funded MOON study was designed to follow ACLR patients after surgery to determine their clinical outcomes including risk factors for the initiation and progression of PTOA. The MOON cohort is unique in the world with >3500 participants and greater than 80% follow-up at 2, 6, and 10 years. The MOON group has published extensively on multivariable modeling on risk factors for patient reported outcomes measures (PROMs), and infrequent outcomes (graft failure, infection, total knee arthroplasty). Further, a novel nested cohort (n=425) was initiated within the MOON cohort which consists of young active patients with a comprehensive research evaluation including radiographs, physical and instrumented laxity examination, and functional testing. In this study, we will add state-of-the-art qMRI to this nested cohort to evaluate cartilage (thickness and matrix composition T1r and T2), bone (3D shape modeling), muscle (volume and fatty infiltration), and other OA-related lesions. The overarching goal of the study is to characterize long-term structural damage and articular cartilage degeneration after ACLR, understand their patterns and relationship to patient outcomes, and identify modifiable predictors for PTOA at 10 years after ACLR from pre-operative and early postoperative time points. Furthermore, the MRI measures, such as cartilage T1r and T2, at 10 years will also serve as potential predictors for future PTOA development (for those who do not develop PTOA at 10 years), failure of the ACLR graft or contralateral ACL, and additional arthroscopic surgery at the 20 years post-ACLR MOON time point. The proposed study will leverage resources from the NIH funded MOON grant, and this is a unique, first ever, opportunity to comprehensively evaluate the knee structural damage and their interrelationship with patient outcomes at 10 years after ACLR in a prospective, well characterized and closely monitored cohort. By identifying modifiable predictors of structural damage at 10 years after ACLR from baseline and early postoperative time points, this study can have immediate impact on improving patient management and treatment, as well as lead to further RCT on identified modifiable risk factors to reduce and prevent PTOA following ACLR.